Mary Leonard, MD, MSCE is an Associate Professor of Pediatrics and Epidemiology applying to renew her Mid-Career Award in Patient Oriented Research (K24). She has an outstanding record of mentorship, leadership and research productivity. During the initial four years of the K24 award, she served as the primary mentor for two funded and two pending K23 applications (submitted 2011), the co-mentor for an additional K23 recipient and the mentor for a K12 Pediatric Scientist Development Award recipient. In addition, she chaired the MSCE thesis committee for 8 physician fellows, served on the thesis committees for 3 PhD students supported by the Renal Biostatistics T32 grant, and mentored 6 medical students supported by research foundations. She mentored two junior investigators in successful R01 applications, and six additional K23 or K25 recipients in ancillary studies, manuscripts and grant applications. Her mentees published 25 first-author manuscripts under her leadership. The overarching goal of this K24 application is to provide the candidate with continued support to lead her multidisciplinary research program, mentor junior investigators in patient oriented research (POR), and develop interventions to improve clinical outcomes in chronic kidney disease (CKD). Improved strategies for the prevention of CKD are urgently needed. Vitamin D deficiency may contribute directly to kidney damage by promoting inflammation and fibrosis, and accelerating podocyte injury and apoptosis. A primary objective of the initial K24 award was to assess vitamin D status and physical function in CKD. The preliminary results subsequently supported the candidate's successful R01 application, Vitamin D Deficiency, Physical Performance and Cardiovascular Outcomes in the Chronic Renal Insufficiency Cohort Study (CRIC). These data suggested that lower 25(OH) vitamin D levels at Year 1 were associated with greater risk of CKD progression, and documented striking increases in vitamin D supplement use by CRIC participants. The proposed New Research in this K24 renewal will identify associations between annual measures of 25(OH) vitamin D levels and progression of CKD within the CRIC cohort of 3939 participants. Innovations include the use of a case-cohort design (the first in CRIC), annual measures of 25(OH)D, FGF-23 and phosphorus levels that will capture cumulative effects over a 4-year interval, and assessment of the effects of vitamin D binding protein to potentially modify the association between 25(OH)D levels and CKD progression. The data generated by the candidate's ongoing and proposed studies of vitamin D metabolism in CRIC, combined with the resources in the Center for Clinical Epidemiology and Biostatistics, will continue to provide a wealth of opportunities to attract new investigators to POR and foster the next generation of clinical investigators in nephrology. PUBLIC HEALTH RELEVANCE: Chronic kidney disease (CKD) affects more than 10 million Americans and poses an enormous financial burden on the US health care system; therefore, strategies for the prevention and treatment of CKD complications are vitally important. Dr. Leonard proposes to renew her K24 funding to continue her productive mentorship of junior clinical investigators in studies related to CKD and its complications. The research aims in this application expand on her research in vitamin D metabolism in CKD to address the role of vitamin D deficiency in the progression of renal injury in CKD.